Crews were called at 8.40pm to a suspected arson at the former Overdale School, on Hawthorn Walk, Eastfield.
Five pumps and an aerial ladder, from Scarborough, Filey, Robin Hood's Bay, Sherburn and Pickering, are at the scene, trying to bring the major fire under control.
It is believed that nearby residents have been told to stay indoors.
The building is no longer in use. Last year a new £6m Overdale School opened at Middle Deepdale, which is twice the size of the old one.
Video: Rebecca Howitt.
